The Spurs supporters were spending time in a local nightspot when a group of hooligans began throwing missiles at the windows in scenes described as "manic" by an eyewitness.
The pub in question, the Smoking Dog, is an English-style bar in Lyon's Old Town and was, according to reports, filled with around 140 fans of the north London club.
The attack, which occurred around 24 hours before Andre Villas-Boas' side meets the Ligue 1 outfit in the Europa League last 32, saw several windows broken by force and fans injured by the flying glass.
Theo Benneworth, who was in the Smoking Dog pub with a group of Spurs fans when the attacks happened, told Goal.com how the violence came in two separate waves.
He said: "We were standing at the bar, not more than 10 feet from the front door, when suddenly the place came under attack. The pub's windows were smashed by an array of chairs, bar stools, tables etc.
"It had really come from nowhere and most people inside the pub seemed taken aback, while a few wanted to fight back. I honestly couldn't tell you how many English fans, if any, went out. The situation really was manic. One British security guard did his best to block incoming items with a bar stool.
"A couple of minutes later, the second wave of missile-throwing came. Less intense this time, but arguably more dangerous as the windows were already smashed through. Along with most others in the pub, I was forced towards the back of the building as everyone was keen to get away from the flying glass. The windows were boarded up quickly and police/ambulances were called.
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The Foreign Office has confirmed that it is looking into the incident.
Spurs fans suffered similar abuse when they traveled to Roma in November, ahead of the clash with Lazio, with reports suggesting that attack might have been the work of an anti-Semitic group.
It is unclear whether the violence in Lyon was religiously or racially motivated, but Christian Radnedge, a Tottenham fan and sports journalist who also witnessed the attacks, told BBC Radio 5 live that the men gave Nazi salutes before the intrusion.
Goal.com's eyewitness Mr. Benneworth added on whether the gang might have been linked to right-wing groups: "All I could see of attackers was mostly black scarves/masks pulled up over faces, and, again, mostly black hoods/baseball caps."
Spurs play Lyon on Thursday evening and take a 2-1 lead from the first leg at White Hart Lane to the Stade de Gerland.